'Ecstasy' May Cause Long-Term Changes in Brain Chemistry

Lower levels of serotonin found in women who had used 'rave' drug up to two years earlier

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TUESDAY, Dec. 13, 2011 (HealthDay News) -- Recreational use of the illegal drug known as ecstasy is associated with long-term changes in brain chemistry, a small, new study reveals.

Based on research with women, it appears that the so-called "rave" drug can induce a drop in serotonin levels that can last up to two years. Serotonin, the research team noted, is critical to the regulation of mood, appetite, sleep, learning and memory.

"We've always known that ecstasy produced transient effects, but with the suggestion that there would be recovery over time," explained study co-author Dr. Ronald Cowan, an associate professor of psychiatry in the department of psychiatry with Vanderbilt University Medical Center's School of Medicine in Nashville, Tenn. "But here we find that these effects may be sustained over time with no evidence of reversal," he added.

"Now this is an observational study, so we can't do really any more than suggest causation," Cowan noted. "But I would say that this is nevertheless the strongest evidence we have that there is chronic change in serotonin levels for those who use the drug."

Cowan and his colleagues report their findings in the Dec. 5 online issue of the Archives of General Psychiatry.

The authors noted that nearly 16 million Americans aged 12 and older have reportedly used ecstasy at some point in their life.

As described by the U.S. National Institute on Drug Abuse, ecstasy (otherwise known by its chemical name, MDMA) is a psychoactive stimulant that is similar in structure to methamphetamine and mescaline.

The drug increases serotonin levels in the brain, and users feel a sense of euphoria and emotional warmth. On the downside, the institute notes that the drug prompts a potentially problematic increase in both heart rate and blood pressure, and can lead to sleep disturbance and lingering feelings of confusion, depression and anxiety.

On the other end of the spectrum, some researchers have pointed to the therapeutic potential for the controlled, clinical use of MDMA to help patients struggling with post-traumatic stress disorder (PTSD) and/or dysfunctional social skills.

Cowan's team focused on 24 women, including 14 who were described as MDMA users. The study was confined to women to avoid the complication of gender-specific serotonin level differences between men and women.

The average age of the women was 22. Cowan noted that those who were MDMA users had taken ecstasy for a period of between three to four years, with the number of pills taken ranging from just five to roughly 375 overall. At the start of the study, all had abstained from ecstasy use for a minimum of 90 days, with the average length of abstinence hovering at the two-year mark.

The team used positron emission tomography (PET) scans to assess levels of serotonin receptors in the participants' brains, noting that receptor levels are known to go up as serotonin levels go down. Those women who had a history of taking ecstasy had higher receptor levels than women who hadn't, suggesting a drop in serotonin levels among MDMA users.

What's more, the team observed a dose-dependent impact: The more ecstasy a woman had taken in her lifetime, the higher her receptor levels.

"We don't actually know what the implications are," acknowledged Cowan. "There is some evidence in prior research that a drop in serotonin leads to sleep apnea, depression, anxiety and memory loss. But in our work we didn't find evidence of mental health issues. No increased anxiety, impulsivity or depression. And the IQs of the women who took the drug were identical with those who had never taken it," he stated.

"We also have no proof that a drop in serotonin levels would be forever," Cowan noted. "Animal studies have indicated that there could be as much as a seven-year duration in such dips. But we don't know. So, this work raises serious concerns and questions, but more research is needed."

Michael Mithoefer, a clinical researcher in the field of MDMA-assisted psychotherapy for PTSD, stressed "the importance of not jumping to conclusions."

"You have to be careful with research like this," Mithoefer cautioned. "There have been some other similar studies suggesting the possibility of some long-term changes with ecstasy use. But the problem with retrospective studies based on self-report is that there are other factors at play that might not be accounted for. Did these people take other drugs at the same time? Was it really MDMA that they took? Exactly how much did they take? What really was the dose taken? That kind of thing can become very unclear when you're asking people to remember past behavior," he explained.

"It's also the case that in clinical research conducted with a few different doses of pure MDMA we have no found evidence of these kinds of problems," noted Mithoefer.

"I do, however, think it's important that people not think that MDMA is without risk," he added. "Especially with recreational use in an uncontrolled setting. Whether that will lead to mental health issues or not is unclear. But it is certainly something that bears further study."